lung cancer
Download
Skip this Video
Download Presentation
Lung Cancer

Loading in 2 Seconds...

play fullscreen
1 / 48

Lung Cancer - PowerPoint PPT Presentation


  • 374 Views
  • Uploaded on

Lung Cancer. R. Zenhäusern. Lung cancer: Epidemiology. Most common cancer in the world 2./ 3. most cancer in men / women 1.2 million new cases / year 1.1 million deaths / year Incidence Men 1940-80: 10  70/100000/J Women 1965-: 5  30/100000/J. Lung cancer: Epidemiology.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Lung Cancer' - Jimmy


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
lung cancer

Lung Cancer

R. Zenhäusern

lung cancer epidemiology
Lung cancer: Epidemiology
  • Most common cancer in the world
    • 2./ 3. most cancer in men / women
  • 1.2 million new cases / year
  • 1.1 million deaths / year
  • Incidence
    • Men 1940-80: 10  70/100000/J
    • Women 1965-: 5  30/100000/J
lung cancer epidemiology3
Lung cancer: Epidemiology
  • 13% of cancers,
  • 18% of cancer deaths
  • Switzerland 3500 new cases / year
  • 80% die during the first year
  • Prognosis remains dismal:
    • five-year survival 10-14%
non small cell lung cancer
Non-Small-Cell Lung Cancer
  • 75 % of all lung cancers
  • Majority of patients present with stage III and IV
nsclc histology
NSCLC: Histology
  • Squamos-cell carcinoma 20-25%
  • Adenocarcinoma 40%
  • Large cell carcinoma 10%
nsclc staging
NSCLC: Staging
  • Staging Locoregional Disease:
    • Chest x-ray and chest CT scan

(including liver and adrenal glands)

    • No evidence of distant metastatic disease: FDG-PET ist recommended
    • Biopsy of mediastinal LN ist recommended:

CT-scan > 1.0 cm or positive on PET

neg. PET scanning does not preclude biopsy

ASCO Guideline 2004;22:330

nsclc staging10
NSCLC: Staging
  • Staging Distant Metastatic Disease:
    • No evidence of distant metastatic disease on CT scan of the chest: PET ist recommended
    • A bone scan is optional
    • Resectable primary lung lesion and bone lesion on PET/bone scan: MRI/CT and biopsy
    • Brain: CT or MRI if symptoms, patients with stage III considered for aggressive local Th.
    • Isolated adrenal mass: biopsy
    • Isolated liver mass: biopsy

ASCO Guideline 2004;22:330

local nsclc stage i ii
Local NSCLC: Stage I, II
  • Standard of care = Surgery
  • Relapse rate 35%-50% in St. I
  • Relapse rate 40%-60% in St. II
  • Adjuvant radiotherapy ?
  • Adjuvant chemotherapy ?
adjuvant radiotherapy
Adjuvant Radiotherapy
  • Port meta-analysis Trialist Group. Lancet 1998;352:257
    • 9 randomised trials of postoperative RT versus surgery

(2128 patients)

    • 21% relative increase in the risk of death with RT
    • Reduction of OS from 55% to 48% (at 2 years)
    • Adverse effect was greatest for Stage I,II
    • St.III (N2): no clear evidence of an adverse effect
adjuvant radiotherapy14
Adjuvant Radiotherapy
  • Conclusion
    • Postoperative RT should not be used outside of a clinical trial in Stage I, II lung cancer, unless surgical margins are positive and repeated resection is not feasible.
adjuvant chemotherapy
Adjuvant Chemotherapy
  • Undetectable microscopic metastasis at diagnosis
  • Individual trials have not shown a significant benefit
  • Meta-analysis BMJ 1995;311:899:
    • Alkylating agents had an adverse effect
    • Cisplatin-based therapy:

13% reduction in risk of death (not significant)

postoperative chemo and radiotherapy
Postoperative Chemo- and Radiotherapy
  • ECOG-Trial: 488 patients with stage II, IIIA
  • RT alone (50.4 Gy) versus

RT + 4x Cisplatin/Etoposid

  • Median survival 39 vs 38 months (ns)
  • TRM 1.2 vs 1.6%
  • Local recurrence 13 vs 12%

Keller et al. NEJM 2000;343:1217

cisplatin based adjuvant chemotherapy international adjuvant lung cancer trial collaboratvie group
Cisplatin-based Adjuvant Chemotherapy(International Adjuvant Lung Cancer Trial Collaboratvie Group)
  • Randomised trial of 3-4 cycles of cisplatin-based CT vs observation in patients with St. II, III LC

CT no CT

5-Y. DFS 39.4% 34.3% p <0.03

5-y. OS 44.5% 40.4%p <0.03

IALT. NEJM 2004;350:351

slide18

Overall Survival (Panel A) and Disease-free Survival (Panel B)

The International Adjuvant Lung Cancer Trial Collaborative Group, N Engl J Med 2004;350:351-360

adjuvant chemotherapy19
Adjuvant Chemotherapy
  • Conclusion:
    • One should consider the use of adjuvant platinum-based chemotherapy in patients with stage I,II or IIA NSCLC
locally advanced nsclc
Locally advanced NSCLC
  • Thoracic irradiation is the mainstay of treatment for inoperable stage III disease
  • Its curative potential is extremely poor

5-year survival rates 3-5%

locally advanced nsclc21
Locally advanced NSCLC
  • A meta-analysis of 22 randomised studies showed a beneficial effect of CT added to RT
    • 10% reduction in risk of death per year
    • Small absolute survival benefit:

4% after 2 years

2% after 5 years

NSCLC Collaborative Group. BMJ 1995;311:899

combined chemotherapy and radiation
Combined chemotherapy and radiation
  • Sequential strategies
    • Primary CT C C.. R R R R R
    • Primary and adjuvant CT C C.. R R R R R C C
  • Concomitant Strategies
    • Daily CT C C C C C C C C C C

R R R R R R R R R R

    • Intermittent CT C.. C..

R R R R R R R R R R

  • Combined Strategies
    • Primary and concomitant CT C...

C C.. R R R R R

therapeutic strategies
Sequential CT–RT

+ CT in standard dose

 of micrometastasis

 volume of primary tumor

- longer treatment time

delay of RT

Concomittant C-RT

+Improvement of local control

(radiosensitisation)

- greater toxic effects

Reduced dose of CT

Therapeutic Strategies
sequential chemo and radiotherapy
Sequential chemo- and radiotherapy
  • Studies performed in the 1980s did not show an advantage
  • Three large phase III trials gave pos. Results
    • Dillman etal. NEJM 1990;329:940
    • Sause et al. JNCI 1995;87:198
    • Le Chevalier et al. JNCI 1992;8:58
sequential chemo and radiotherapy25
Sequential chemo- and radiotherapy

Dillman etal. NEJM 1990;329:940 (CALGB 8433)

2 cycles of Cis / Vbl  RT (60 Gy/6 w)

R

RT (60 Gy/6 w)

results sequential ct and rt
Results: Sequential CT and RT

Med. S 2y-S 3y-S 7y-S (%)

CT-RT 14 mo 26 23 17

RT 10 mo 13 11 6

Dillman etal. NEJM 1990;329:940

Dillman et al. JNCI 1996;88:1210

results sequential ct and rt27
Results: Sequential CT and RT
  • US intergroup trialSause W. JNCI 1995;87:198

n=458Sause W. Chest 2000;117:351

MS (mo) 5y-S (%)

RT 11.4 5

2x Cis/Vbl 13.2 8

hyper RT 12 6

  • French trialLe Chevalier JNCI 1992;8:58

N=353

3x CT  RT vs RT 3y-S 12% vs 4%

concomitant chemo and radiotherapy
Simultaneous CT / RT is beneficial in:

Head and neck cancer

Anal cancer

Cervical cancer

Cisplatin is effective as a radiosensitiser

6-8 mg/m2 daily

30 mg/m2 weekly

70 mg/m2 3-weekly

Concomitant Chemo- and Radiotherapy
concomitant ct rt eortc trial
Concomitant CT-RT: EORTC Trial
  • Schaake-Koning C. NEJM 1992;326:524

331 patients randomised to one of three regimens:

    • RT alone: 30 Gy in 10 fractions, 3-week rest period,

25 Gy in 10 fractions

    • RT + daily cisplatin (6-8 mg/m2)
    • RT + weekly cisplatin (30 mg/m2)
eortc trial results
EORTC Trial: Results

2-year Survival

  • RT alone: 13%
  • RT + daily cisplatin: 26%
  • RT + weekly cisplatin: 18%

Schaake-Koning C. NEJM 1992;326:524

sequential versus concomitant ct rt
Sequential versus concomitant CT-RT
  • Japanese study:Furuse K et al. JCO 1999;17:2692

n= 320 MS (mo) 5y-DFS

-2 cycles MVC  RT 56 Gy 13.3 19%

-MCV/RT-10 days rest-MVC/RT 16.5 27%

  • RTOG 9410: Curran WJ. ASCO 2003;22:a621

n=611

2xCVRT(60Gy) vs CV/RT OS: 4 vs 25% p= 0.046

neoadjuvant therapy
Neoadjuvant Therapy
  • Pancoast`s tumor, vertebral invasion
    • Combined neoadjuvant CT-RT should be considered
  • Tumors with ipsilateral mediastinal spread (N2)
    • Poor survival with surgery alone
    • 2 small randomised trials showed a benefit of neoadjuvant combined CT-RT
    • Roth et al. JNCI 1994;86:673
    • Phase II trials report good results of neoadjuvant CT§
sakk studies
SAKK Studies
  • SAKK 16/00
    • Preoperative CRT vs CT in NSCLC stage IIIA
    • CT: 3 cycles docetaxel and cisplatin (D1,22,43)
    • RT: 3 weeks of RT (44 Gy in 22 fractions)
  • SAKK 16/01
    • Preoperative CRT in NSCLC pts with operable stage IIIB disease
    • The same regimen as 16/00
metastasis
Metastasis

40-50% at diagnosis

70% during follow-up

chremotherapy for nsclc
Old agents

Cisplatin

Carboplatin

Etoposid

Vinblastin

New agents

Docetaxel

Paclitaxel

Vinorelbine

Gemcitabine

Irinotecan

Chremotherapy for NSCLC
nsclc chemotherapy combinations
Regimes

Cisplatin+Paclitaxel

Cisplatin+Gemcitabine

Cisplatin+Docetaxel

Carboplatin+paclitaxel

Results (n=1155 pts.)

Response rate 19%

Median survival 8 months

1-year survival 33%

2-year survival 11%

Schiller et al. NEJM 2002;346:92

NSCLC: chemotherapy combinations
new agents induction ct followed by concomitant ct rt
New agents: Induction CT followed by concomitant CT-RT

Induction (2 cycles) Concomitant (2 cycles)

Vinorelbine 25 mg/m2 D1,8,(15) 15 mg/m2 D1,8

Cisplatin 80mg/m2 D1 80mg/m2 D1

Paclitaxel 225 mg/m2 D1 135 mg/m2 D1

Cisplatin 80mg/m2 D1 80mg/m2 D1

Gemcitabine 1250 mg/m2 D1,8 600 mg/m2 D1,8

Cisplatin 80mg/m2 D1 80mg/m2 D1

CALGB study 9431: Vokes et al. JCO 2002;20:4191

new agents induction ct followed by concomitant ct rt39
New agents: Induction CT followed by concomitant CT-RT

RR(CT) RR(CT-RT) 1yS 2yS 3yS

(%)

V+C 44% 73% 65 40 23

P+C 33% 67% 62 29 19

G+C 40% 74% 68 37 28

CALGB study 9431: Vokes et al. JCO 2002;20:4191

conclusion combined modality therapy for stage iii disease
Conclusion: Combined-Modality Therapy for Stage III Disease
  • Adding CT to radiation therapy improves survival and alters the course of this disease
  • Phase III studies suggest improvement in both local control and survival with concomitant CT-RT
  • Combined CT-RT should be the standard of care of patients with good PS and minimal weight loss
  • The absolute gain from combined CT-RT is still modest
  • The role of surgery following induction CT-RT is for patients with unresectable Cancer is being explored
small cell lung cancer sclc
Small-cell Lung Cancer (SCLC)
  • 15-20% of all lung cancer
  • Incidence: 15/100000/year
  • Men : women = 5 : 1
slide42
SCLC
  • Rapid local and metastatic spread
  • Mediastinal lymph node metastasis in most cases
  • Median Survival in untreated patients 2-3 months
  • Superior vena caval obstruction and paraneoplastic syndromes (SIADH, Cushing)
  • Association with smoking
sclc staging
Limited Disease

Confined to:

One hemithorax

Mediastinum

Ipislateral hilar and supraclavicular nodes

Extensive Disease

Malignant pleura and pericard effusion

Contralateral hilar and supraclavicular nodes

SCLC Staging
sclc therapy
SCLC Therapy
  • No surgery; SCLC is a systemic disease
  • Chemotherapy is the standard of care
    • Cisplatin+Etoposid
  • Limited stage SCLC: Bimodality therapy with chemotherapy and radiotherapy
sclc therapy45
SCLC Therapy
  • The addition of thoracic RT significantly improves survival in patients with LS-SCLC
    • Meta-analysis. Pignon et al. NEJM 1992;327:1618
    • 14% reduction in the mortality rate
    • 5.4% benefit in terms of OS at 3 years
  • Early use of RT with CT improves cure rates
sclc therapy46
SCLC Therapy
  • The actuarial risk of CNS metastasis developing 2 years after CR of SCLC is 35%-60%
  • Prophylactic cranial Irradiation is recommended for pts. With LS-SCLC in CR
    • Meta-analysis: Auperin et al. NEJM;1999:341:475
    • PCI: 5.4% greater absolute survival at 3 years
sclc results
SCLC Results
  • Limited Disease:
    • Remission rate 80-90%
    • CR 50-60%
    • Median Survival 18-20 months
    • 2-year Survival 40%
    • 5-year Survival 15-25%
sclc results48
SCLC Results
  • Extensive Disease:
    • Remission rate 70-80%
    • CR 20-30%
    • Median Survival 8-10 months
    • 2-year Survival < 10%
ad